Nuevas perspectivas sobre las alteraciones de la red cognitiva en la epilepsia del lóbulo temporal: un estudio de PET con [¹⁸F]SynVesT-1

Current therapeutic interventions towards cognitive deficits in temporal lobe epilepsy (TLE) remain suboptimal due to incomplete elucidation of the underlying pathophysiological mechanisms. Emerging evidence implicates synapse loss as a critical neuropathological substrate associated with cognitive dysfunction. Given that synapse constitute the fundamental structural units of neural circuit and established disruption of cognitive networks in epilepsy, this study innovatively explores epileptic cognitive network alteration from synaptic viewpoint.

Utilizing [¹⁸F]SynVesT-1 positron emission tomography (PET) for in-vivo synaptic density quantification and Kullback-Leibler Divergence Similarity Estimation (KLSE) depicting for individual-level network characterization, we identified synaptic connectome alteration in TLE patients. The relationship between abnormal synaptic connectivity and cognitive assessment scores was evaluated by Spearman correlation analysis.

We observed significant global reduction in edge connectivity and decreased weighted connectivity strength in TLE, which correlates with impaired neuropsychological performance in both intelligence and memory domains respectively. Hypoconnectivity in the frontal lobe and superior temporal gyrus correlated with poorer linguistic intelligence quotient (IQ). The caudate nucleus emerged as a critical hub, with its eigenvector centrality showing positive associations with both spatial skills and full-scale intelligence quotient (FSIQ). Hippocampal-posterior cortical circuitry involving the interaction between the hippocampus and the lingual gyrus, angular gyrus, calcarine fissure, mediated the variance in memory quotient (MQ).

These findings suggest that synaptic connectivity attenuation may serve as a novel biomarker for cognitive deficits in temporal lobe epilepsy, providing an innovative perspective for targeted clinical interventions.